Abstract
Depressed contractility is a central feature of the failing human heart and has been attributed to altered [Ca2+]i. This study examined the respective roles of the L-type Ca2+ current (ICa), SR Ca2+ uptake, storage and release, Ca2+ transport via the Na+-Ca2+ exchanger (NCX), and Ca2+ buffering in the altered Ca2+ transients of failing human ventricular myocytes. Electrophysiological techniques were used to measure and control Vm and measure Im, respectively, and Fluo-3 was used to measure [Ca2+]i in myocytes from nonfailing (NF) and failing (F) human hearts. Ca2+ transients from F myocytes were significantly smaller and decayed more slowly than those from NF hearts. Ca2+ uptake rates by the SR and the amount of Ca2+ stored in the SR were significantly reduced in F myocytes. There were no significant changes in the rate of Ca2+ removal from F myocytes by the NCX, in the density of NCX current as a function of [Ca2+]i, ICa density, or cellular Ca2+ buffering. However, Ca2+ influx during the late portions of the action potential seems able to elevate [Ca2+]i in F but not in NF myocytes. A reduction in the rate of net Ca2+ uptake by the SR slows the decay of the Ca2+ transient and reduces SR Ca2+ stores. This leads to reduced SR Ca2+ release, which induces additional Ca2+ influx during the plateau phase of the action potential, further slowing the decay of the Ca2+ transient. These changes can explain the defective Ca2+ transients of the failing human ventricular myocyte.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 651-658 |
| Number of pages | 8 |
| Journal | Circulation Research |
| Volume | 92 |
| Issue number | 6 |
| DOIs | |
| State | Published - Apr 4 2003 |
| Externally published | Yes |
Fingerprint
Keywords
- Congestive heart failure
- Excitation-contraction coupling
- Na-Ca exchanger
- Sarcoplasmic reticulum
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
Cite this
Cellular basis of abnormal calcium transients of failing human ventricular myocytes. / Piacentino, Valentino; Weber, Christopher R.; Chen, Xiongwen; Weisser-Thomas, Jutta; Margulies, Kenneth B.; Bers, Donald M; Houser, Steven R.
In: Circulation Research, Vol. 92, No. 6, 04.04.2003, p. 651-658.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cellular basis of abnormal calcium transients of failing human ventricular myocytes
AU - Piacentino, Valentino
AU - Weber, Christopher R.
AU - Chen, Xiongwen
AU - Weisser-Thomas, Jutta
AU - Margulies, Kenneth B.
AU - Bers, Donald M
AU - Houser, Steven R.
PY - 2003/4/4
Y1 - 2003/4/4
N2 - Depressed contractility is a central feature of the failing human heart and has been attributed to altered [Ca2+]i. This study examined the respective roles of the L-type Ca2+ current (ICa), SR Ca2+ uptake, storage and release, Ca2+ transport via the Na+-Ca2+ exchanger (NCX), and Ca2+ buffering in the altered Ca2+ transients of failing human ventricular myocytes. Electrophysiological techniques were used to measure and control Vm and measure Im, respectively, and Fluo-3 was used to measure [Ca2+]i in myocytes from nonfailing (NF) and failing (F) human hearts. Ca2+ transients from F myocytes were significantly smaller and decayed more slowly than those from NF hearts. Ca2+ uptake rates by the SR and the amount of Ca2+ stored in the SR were significantly reduced in F myocytes. There were no significant changes in the rate of Ca2+ removal from F myocytes by the NCX, in the density of NCX current as a function of [Ca2+]i, ICa density, or cellular Ca2+ buffering. However, Ca2+ influx during the late portions of the action potential seems able to elevate [Ca2+]i in F but not in NF myocytes. A reduction in the rate of net Ca2+ uptake by the SR slows the decay of the Ca2+ transient and reduces SR Ca2+ stores. This leads to reduced SR Ca2+ release, which induces additional Ca2+ influx during the plateau phase of the action potential, further slowing the decay of the Ca2+ transient. These changes can explain the defective Ca2+ transients of the failing human ventricular myocyte.
AB - Depressed contractility is a central feature of the failing human heart and has been attributed to altered [Ca2+]i. This study examined the respective roles of the L-type Ca2+ current (ICa), SR Ca2+ uptake, storage and release, Ca2+ transport via the Na+-Ca2+ exchanger (NCX), and Ca2+ buffering in the altered Ca2+ transients of failing human ventricular myocytes. Electrophysiological techniques were used to measure and control Vm and measure Im, respectively, and Fluo-3 was used to measure [Ca2+]i in myocytes from nonfailing (NF) and failing (F) human hearts. Ca2+ transients from F myocytes were significantly smaller and decayed more slowly than those from NF hearts. Ca2+ uptake rates by the SR and the amount of Ca2+ stored in the SR were significantly reduced in F myocytes. There were no significant changes in the rate of Ca2+ removal from F myocytes by the NCX, in the density of NCX current as a function of [Ca2+]i, ICa density, or cellular Ca2+ buffering. However, Ca2+ influx during the late portions of the action potential seems able to elevate [Ca2+]i in F but not in NF myocytes. A reduction in the rate of net Ca2+ uptake by the SR slows the decay of the Ca2+ transient and reduces SR Ca2+ stores. This leads to reduced SR Ca2+ release, which induces additional Ca2+ influx during the plateau phase of the action potential, further slowing the decay of the Ca2+ transient. These changes can explain the defective Ca2+ transients of the failing human ventricular myocyte.
KW - Congestive heart failure
KW - Excitation-contraction coupling
KW - Na-Ca exchanger
KW - Sarcoplasmic reticulum
UR - http://www.scopus.com/inward/record.url?scp=0344284562&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0344284562&partnerID=8YFLogxK
U2 - 10.1161/01.RES.0000062469.83985.9B
DO - 10.1161/01.RES.0000062469.83985.9B
M3 - Article
C2 - 12600875
AN - SCOPUS:0344284562
VL - 92
SP - 651
EP - 658
JO - Circulation Research
JF - Circulation Research
SN - 0009-7330
IS - 6
ER -